Orphan Nuclear Receptors: The Exotics of Xenobiotics
Open accessAbstract
nuclear receptor constitutive androstane receptor cytochrome P450 phenobarbital pregnenolone 16α-carbonitrile pregnane X receptor rifampicin steroid and xenobiotic receptor 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene retinoid X receptor Orphan nuclear receptors (NRs)1 include gene products that are structurally related to nuclear hormone receptors but lack known physiological ligands. It has become clear that orphan NRs represent a unique and pivotal resource to uncover new regulatory systems that impact both health and human diseases. In addition to production and clearance of endogenous hormones, mammals also confront numerous foreign chemicals (xenobiotics) such as ingested food, environmental pollutants, and carcinogens as well as prescription and non-prescription drugs. Such compounds may accumulate to toxic levels unless they are metabolized and eliminated, a process largely mediated by the supergene family of cytochrome P450 (CYP) enzymes. Expressed mainly in the liver and capable of recognizing an amazing diversity of xenobiotics, CYP enzymes catalyze the metabolic conversion of xenobiotics to polar derivatives that are more readily eliminated (for reviews, see Refs. 1Gonzalez F.J. Trends Pharmacol. Sci. 1992; 13: 346-352Abstract Full Text PDF PubMed Scopus (393) Google Scholar and 2Denison M.S. Whitlock Jr., J.P. J. Biol. Chem. 1995; 270: 18175-18178Abstract Full Text Full Text PDF PubMed Scopus (333) Google Scholar). Thus, CYP enzymes, especially members of the CYP 1–4 families, are crucial for xenobiotic detoxification and survival of organisms (for a review, see Ref. 3Waxman D.J. Arch. Biochem. Biophys. 1999; 369: 11-23Crossref PubMed Scopus (674) Google Scholar). Among CYP enzymes, the CYP3A and -2B isoenzymes are of particular medical significance. For example, the human CYP3A4 enzyme alone is involved in the metabolism of 50–60% of clinical drugs as well as neutraceuticals and herbal medicines (4Maurel P. Ioannides C. Cytochrome P450, Metabolic and Toxicological Aspects. CRC Press, Inc., Boca Raton, FL1996: 241-270Google Scholar). An additional 25–30% of these compounds are metabolized by the CYP2B isoenzymes. The combined metabolic versatility of CYP3A and -2B, coupled with their inducibility by xenobiotic substrates, constitutes a molecular basis for many clinical drug-drug interactions (4Maurel P. Ioannides C. Cytochrome P450, Metabolic and Toxicological Aspects. CRC Press, Inc., Boca Raton, FL1996: 241-270Google Scholar). Compounds that are strong CYP enzyme inducers such as glucocorticoids, phenobarbital (PB), or rifampicin (RIF) can dramatically affect the clearance of any co-consumed drug that is a substrate for the enzyme. Recently, St. Johns wort, a popular herbal remedy for depression, was found to trigger severe adverse drug-drug interactions with oral contraceptives, the HIV protease inhibitor indinavir, and the immunosuppressant cyclosporin as a consequence of activating the CYP3A system (Ref. 5Moore L.B. Goodwin B. Jones S.A. Wisely G.B. Serabjit-Singh C.J. Willson T.M. Collins J.L. Kliewer S.A. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 7500-7502Crossref PubMed Scopus (885) Google Scholar, and references therein). In 1992, the aryl hydrocarbon receptor was identified as a transcriptional sensor mediating the induction of CYP1A and -1B1 genes by dioxin and a variety of related polycyclic aromatic hydrocarbons (6Ema M. Sogawa K. Watanabe N. Chujoh Y. Matsushita N. Gotoh O. Funae Y. Fujii-Kuriyama Y. Biochem. Biophys. Res. Commun. 1992; 184: 246-253Crossref PubMed Scopus (371) Google Scholar). Aryl hydrocarbon receptor is a member of the basic helix-loop-helix family of transcription factors, and it was presumed that other basic helix-loop-helix proteins might control the CYP3A and -2B gene families. This turned out to be an incorrect assumption, and the molecular basis for induction of CYP3A and -2Bgenes remained largely unknown. A major conceptual challenge in defining the molecular mechanisms for xenobiotic response is thatCYP genes are induced by thousands of natural and synthetic compounds, and yet the inducibility of CYP enzymes shows clear target gene and species specificity. For example, the antibiotic RIF has been shown to be a specific CYP3A inducer in humans and rabbits, whereas pregnenolone 16α-carbonitrile (PCN), an anti-glucocorticoid, is a rodent-specific CYP3A inducer (Ref. 7Barwick J.L. Quattrochi L.C. Mills A.S. Potenza C. Tukey R.H. Guzelian P.S. Mol. Pharmacol. 1996; 50: 10-16PubMed Google Scholar, and references therein). Pharmacologic studies in cultured primary hepatocytes suggest that it is not the structure of CYP3A genes but rather species-specific cellular factor(s) that dictates the profile ofCYP3A inducibility (7Barwick J.L. Quattrochi L.C. Mills A.S. Potenza C. Tukey R.H. Guzelian P.S. Mol. Pharmacol. 1996; 50: 10-16PubMed Google Scholar). In the past 3–4 years, emerging evidence has increasingly pointed to a unique role for orphan NRs in the regulation
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Genes homologous to the vertebrate xenobiotic sensors PXR and CAR are absent from the sea urchin genome.
“Genes homologous to the vertebrate xenobiotic sensor NR1I genes [pregnane X receptor, PXR; constitutive androstane receptor, CAR (46)] are absent”
From The Genome of the Sea Urchin <i>Strongylocentrotus purpuratus</i> (2006) · cites this paper as [46]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
An Orphan Nuclear Receptor Activated by Pregnanes Defines a Novel Steroid Signaling Pathway
Kliewer, S. A., Moore, J. T., Wade, L., Staudinger, J. L., Watson, M. A., Jones, S. A., McKee, D. D., Oliver, B. B., Willson, T. M., Zetterström, R. H., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)80900-9 · Cited by 1,534 · see citing works
The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity
Staudinger, J. L., Goodwin, B. J., Jones, S. A., Hawkins‐Brown, D., MacKenzie, K. I., Latour, A. M., Liu, Y., Klaassen, C. D., Brown, K. K., Reinhard, J. F., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051551698 · Cited by 1,378 · see citing works
St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor
Moore, L. B., Goodwin, B. J., Jones, S. A., Wisely, G. B., Serabjit‐Singh, C. J., Willson, T. M., Collins, J. L., & Kliewer, S. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.130155097 · Cited by 946 · see citing works
SXR, a novel steroid and xenobioticsensing nuclear receptorPreprint
Blumberg, B., Sabbagh, W., Juguilon, H., Bolado, J., van Meter, C. M., Ong, E. S., & Evans, R. M. (1998) · Genes & Development · doi:10.1101/gad.12.20.3195 · Cited by 912 · see citing works
Self-citationIdentification of a human nuclear receptor defines a new signaling pathway for CYP 3 A induction
Bertilsson, G., Heidrich, J., Svensson, K., Åsman, M., Jendeberg, L., Sydow‐Báckman, M., OHLSSON, R. I., Postlind, H., Blomquist, P., & Berkenstam, A. L. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.21.12208 · Cited by 873 · see citing works
The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux
Synold, T. W., Dussault, I., & FORMAN, B. M. (2001) · Nature Medicine · doi:10.1038/87912 · Cited by 840 · see citing works
Moore, L. B., Parks, D. J., Jones, S. A., Bledsoe, R. K., Consler, T. G., Stimmel, J. B., Goodwin, B. J., Liddle, C., Blanchard, S. G., Willson, T. M., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001215200 · Cited by 818 · see citing works
Waxman, D. J. (1999) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1999.1351 · Cited by 754 · see citing works
An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids
Xie, W., Radominska-p, A., Shi, Y., Simon, C. M., Nelson, M. C., Ong, E. S., Waxman, D. J., & Evans, R. M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051014398 · Cited by 751 · see citing works
Self-citationHonkakoski, P., Zelko, I. N., Sueyoshi, T., & Negishi, M. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.10.5652 · Cited by 701 · see citing works
Humanized xenobiotic response in mice expressing nuclear receptor SXR
Xie, W., Barwick, J. L., Downes, M., Blumberg, B., Simon, C. M., Nelson, M. C., Neuschwander‐Tetri, B. A., Brunt, E. M., Guzelian, P. S., & Evans, R. M. (2000) · Nature · doi:10.1038/35019116 · Cited by 661 · see citing works
Self-citationThe nuclear receptor CAR mediates specific xenobiotic induction of drug metabolism
Wei, P., Zhang, J., Egan-Hafley, M., Liang, S., & Moore, D. D. (2000) · Nature · doi:10.1038/35038112 · Cited by 654 · see citing works
Reciprocal activation of Xenobiotic response genes by nuclear receptors SXR/PXR and CARPreprint
Xie, W., Barwick, J. L., Simon, C. M., Pierce, A. M., Safe, S. H., Blumberg, B., Guzelian, P. S., & Evans, R. M. (2000) · Genes & Development · doi:10.1101/gad.846800 · Cited by 510 · see citing works
Self-citationBaes, M. I., Gulick, T., Choi, H.-S., Martinoli, M., Simha, D., & Moore, D. D. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.3.1544 · Cited by 492 · see citing works
Androstane metabolites bind to and deactivate the nuclear receptor CAR-β
FORMAN, B. M., Tzameli, I., Choi, H., Chen, J., Simha, D., Seol, W., Evans, R. M., & Moore, D. D. (1998) · Nature · doi:10.1038/26996 · Cited by 476 · see citing works
Self-citationTzameli, I., Pissios, P., Schuetz, E. G., & Moore, D. D. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.9.2951-2958.2000 · Cited by 409 · see citing works
cDNA cloning and structure of mouse putative Ah receptor
Ema, M., Sogawa, K., Watanabe, N., Chujoh, Y., Matsushita, N., Gotoh, O., Funae, Y., & Fujii-Kuriyama, Y. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)91185-s · Cited by 395 · see citing works
Human cytochromes P450: problems and prospects
Gonzalez, F. J. (1992) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(92)90107-h · Cited by 365 · see citing works
Xenobiotic-inducible Transcription of Cytochrome P450 Genes
Denison, M. S., & Whitlock, J. P. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.31.18175 · Cited by 354 · see citing works
Orphan nuclear receptors—new ligands and new possibilities: Figure 1.Preprint
Blumberg, B., & Evans, R. M. (1998) · Genes & Development · doi:10.1101/gad.12.20.3149 · Cited by 301 · see citing works
Self-citationWan, Y. Y., An, D., Cai, Y., Repa, J. J., Chen, T. H.-P., Flores, M., Postic, C., Magnuson, M. A., Chen, J., Chien, K. R., et al. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.12.4436-4444.2000 · Cited by 226 · see citing works
[42] Use of human hepatocytes to study P450 gene induction
Strom, S. C., Pisarov, L. A., Dorko, K., Thompson, M. T., Schuetz, J. D., & Schuetz, E. G. (1996) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(96)72044-x · Cited by 174 · see citing works
Barwick, J. L., Quattrochi, L. C., Mills, A. S., Potenza, C., Tukey, R. H., & Guzelian, P. S. (1996) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)09115-1 · Cited by 134 · see citing works
Savas, Ü., Griffin, K. J., & Johnson, E. F. (1999) · Molecular Pharmacology · doi:10.1124/mol.56.5.851 · Cited by 107 · see citing works
Howell, S. R., Shirley, M. A., & Ulm, E. H. (1998) · PubMed · Cited by 50 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- Maurel, P. (1996) in Cytochrome P450, Metabolic and Toxicological Aspects (Ioannides, C., ed) pp. 241-270, CRC Press, Inc., Boca Raton, FL
- Moore, L. B., Goodwin, B., Jones, S. A., Wisely, G. B., Serabjit-Singh, C. J., Willson, T. M., Collins, J. L., and Kliewer, S. A. (2000) Proc. Natl. Acad. Sci.
- Bertilsson, G., Heidrich, J., Svensson, K., Asman, M., Jendeberg, L., Sydow- Backman, M., Ohlsson, R., Postlind, H., Blomquist, P., and Berkenstam, A. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 12208 -12213
- Staudinger, J. L., Goodwin, B., Jones, S. A., Hawkins-Brown, D., MacKenzie, K. I., LaTour, A., Liu, Y., Klaassen, C. D., Brown, K. K., Reinhard, J., Willson, T. M., Koller, B. H., and Kliewer, S. A. (2001) Proc. Natl. Acad. Sci.
- Xie, W., Radominska-Pandya, A., Shi, Y., Simon, C. M., Nelson, M. C., Ong, E. S., Waxman, D. J., and Evans, R. M. (2001) Proc. Natl. Acad. Sci. U. S. A. 98, 3375-3380
Cited by
Sorted by citations
Nuclear Receptors and Lipid Physiology: Opening the X-Files
Chawla, A., Repa, J. J., Evans, R. M., & Mangelsdorf, D. J. (2001) · Science · doi:10.1126/science.294.5548.1866 · Cited by 2,085 · see citing works
Self-citationLipids and Lipid-Based Formulations: Optimizing the Oral Delivery of Lipophilic Drugs
Porter, C. J. H., Trevaskis, N. L., & Charman, W. N. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2197 · Cited by 1,824 · see citing works
Martignoni, M., Groothuis, G. M. M., & de Kanter, R. (2006) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2.6.875 · Cited by 1,478 · see citing works
The Genome of the Sea Urchin <i>Strongylocentrotus purpuratus</i>
Sodergren, E., Weinstock, G. M., Davidson, E. H., Cameron, R. A., Gibbs, R. A., Angerer, R. C., Angerer, L. M., Arnone, M. I., Burgess, D. R., Burke, R. D., et al. (2006) · Science · doi:10.1126/science.1133609 · Cited by 1,132 · see citing works
Bile salt transporters: molecular characterization, function, and regulation
Trauner, M., & Boyer, J. L. (2003) · Physiological Reviews · doi:10.1152/physrev.00027.2002 · Cited by 999 · see citing works
Nuclear Receptors and the Control of Metabolism
Francis, G. A., Fayard, E., Picard, F., & Auwerx, J. H. (2003) · Annual Review of Physiology · doi:10.1146/annurev.physiol.65.092101.142528 · Cited by 632 · see citing works
Cancer Chemoprevention by Carotenoids
Tanaka, T., Shnimizu, M., & Moriwaki, H. (2012) · Molecules · doi:10.3390/molecules17033202 · Cited by 590 · see citing works
Regulation of bile acid synthesis: pathways, nuclear receptors, and mechanisms
Chiang, J. Y. L. (2003) · Journal of Hepatology · doi:10.1016/j.jhep.2003.11.006 · Cited by 550 · see citing works
Mechanism-Based Inhibition of Cytochrome P450 3A4 by Therapeutic Drugs
Zhou, S., Chan, S. Y., Goh, B. C., Chan, E., Duan, W., Huang, M., & McLeod, H. L. (2005) · Clinical Pharmacokinetics · doi:10.2165/00003088-200544030-00005 · Cited by 512 · see citing works
Grefhorst, A., Elzinga, B. M., Voshol, P. J., Plösch, T., Kok, T., Bloks, V. W., van der Sluijs, F. H., Havekes, L. M., Romijn, J. A., Verkade, H. J., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204887200 · Cited by 502 · see citing works
Induction of Drug Metabolism: The Role of Nuclear Receptors
Handschin, C., & Meyer, U. (2003) · Pharmacological Reviews · doi:10.1124/pr.55.4.2 · Cited by 467 · see citing works
Interactions of Herbs with Cytochrome P450
Zhou, S., Gao, Y., Jiang, W., Huang, M., Xu, A., & Paxton, J. W. (2003) · Drug Metabolism Reviews · doi:10.1081/dmr-120018248 · Cited by 397 · see citing works
Vitamin K2 Regulation of Bone Homeostasis Is Mediated by the Steroid and Xenobiotic Receptor SXR
Tabb, M. M., Sun, A., Zhou, C., Grün, F., Errandi, J., Romero, K. M., Pham, H., Inoue, S., Mallick, S., Lin, M., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303136200 · Cited by 386 · see citing works
Regulation of drug-metabolizing enzymes by xenobiotic receptors: PXR and CAR
Tolson, A. H., & Wang, H. (2010) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2010.08.006 · Cited by 387 · see citing works
BAREing it all: the adoption of LXR and FXR and their roles in lipid homeostasis
Edwards, P. A., Kast-Woelbern, H. R., & Anisfeld, A. M. (2002) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)30180-2 · Cited by 387 · see citing works
Herbal Modulation of P‐Glycoprotein
Zhou, S., Lim, L. Y., & Chowbay, B. (2004) · Drug Metabolism Reviews · doi:10.1081/dmr-120028427 · Cited by 375 · see citing works
Xie, W., Yeuh, M.-F., Radominska-p, A., Saini, S. P. S., Negishi, Y., Bottroff, B. S., Cabrera, G. Y., Tukey, R. H., & Evans, R. M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0438010100 · Cited by 367 · see citing works
Self-citationMadan, A., Graham, R., Carroll, K. M., Mudra, D. R., Burton, L. A., Krueger, L. A., Downey, A., Czerwiński, M., Forster, J., Ribadeneira, M. D., et al. (2003) · Drug Metabolism and Disposition · doi:10.1124/dmd.31.4.421 · Cited by 338 · see citing works
Kodama, S., Koike, C., Negishi, M., & Yamamoto, Y. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.18.7931-7940.2004 · Cited by 334 · see citing works
Vitamin D: More Than a “Bone-a-Fide” Hormone
Sutton, A. L. M., & MacDonald, P. N. (2003) · Molecular Endocrinology · doi:10.1210/me.2002-0363 · Cited by 295 · see citing works
Regulation of a xenobiotic sulfonation cascade by nuclear pregnane X receptor (PXR)
Sonoda, J., Xie, W., Rosenfeld, J. M., Barwick, J. L., Guzelian, P. S., & Evans, R. M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.212494599 · Cited by 281 · see citing works
Self-citationGoldstone, J. V., Hamdoun, A., Cole, B. J., Howard-Ashby, M., Nebert, D. W., Scally, M., Dean, M., Epel, D., Hahn, M. E., & Stegeman, J. J. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.08.066 · Cited by 280 · see citing works
Role of Orphan Nuclear Receptors in the Regulation of Drug-Metabolising Enzymes
Wang, H., & LeCluyse, E. L. (2003) · Clinical Pharmacokinetics · doi:10.2165/00003088-200342150-00003 · Cited by 278 · see citing works
Drug Interactions with St John???s Wort
Mannel, M. (2004) · Drug Safety · doi:10.2165/00002018-200427110-00003 · Cited by 239 · see citing works
Drug transport proteins in the liver
Faber, K. N., Müller, M. M., & Jansen, P. L. M. (2003) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00173-4 · Cited by 220 · see citing works
Chen, Y., Tang, Y., Guo, C., Wang, J., Boral, D., & Nie, D. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.01.030 · Cited by 218 · see citing works
Wang, H., Faucette, S. R., Sueyoshi, T., Moore, R., Ferguson, S., Negishi, M., & LeCluyse, E. L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212482200 · Cited by 216 · see citing works
Distribution of Receptor Targets in the Lung
Barnes, P. J. (2004) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200409-045ms · Cited by 211 · see citing works
Independent elaboration of steroid hormone signaling pathways in metazoans
Markov, G. V., Tavares, R., Dauphin-Villemant, C., Demeneix, B. A., Baker, M. E., & Laudet, V. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812138106 · Cited by 187 · see citing works
The steroid and xenobiotic receptor (SXR), beyond xenobiotic metabolism
Zhou, C., Verma, S., & Blumberg, B. (2009) · Nuclear Receptor Signaling · doi:10.1621/nrs.07001 · Cited by 178 · see citing works
Lignans, bacteriocides and organochlorine compounds activate the human pregnane X receptor (PXR)
Jacobs, M. N., Nolan, G. T., & Hood, S. R. (2005) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2005.03.015 · Cited by 175 · see citing works
Nuclear receptor regulation of hepatic function
Karpen, S. J. (2002) · Journal of Hepatology · doi:10.1016/s0168-8278(02)00129-0 · Cited by 169 · see citing works
PXR: More Than Just a Master Xenobiotic Receptor
Oladimeji, P. O., & Chen, T. (2017) · Molecular Pharmacology · doi:10.1124/mol.117.110155 · Cited by 166 · see citing works
The Nuclear Pregnane X Receptor Regulates Xenobiotic Detoxification
Kliewer, S. A. (2003) · Journal of Nutrition · doi:10.1093/jn/133.7.2444s · Cited by 165 · see citing works
PXR: A Xenobiotic Receptor of Diverse Function Implicated in Pharmacogenetics
Zhang, B., Xie, W., & Krasowski, M. D. (2008) · Pharmacogenomics · doi:10.2217/14622416.9.11.1695 · Cited by 160 · see citing works
Self-citationHernandez, J., Mota, L. C., & Baldwin, W. S. (2009) · Current pharmacogenomics and personalized medicine (Online)/Current pharmacogenomics and personalized medicine · doi:10.2174/187569209788654005 · Cited by 159 · see citing works
Köhle, C., & Bock, K. W. (2008) · Biochemical Pharmacology · doi:10.1016/j.bcp.2008.05.020 · Cited by 151 · see citing works
Miki, Y., Suzuki, T., Kitada, K., Yabuki, N., Shibuya, R., Moriya, T., Ishida, T., Ohuchi, N., Blumberg, B., & Sasano, H. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-1070 · Cited by 142 · see citing works
Miki, Y., Suzuki, T., Tazawa, C., Blumberg, B., & Sasano, H. (2005) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2004.12.005 · Cited by 142 · see citing works
Tabb, M. M., Kholodovych, V. V., Grün, F., Zhou, C., Welsh, W. J., & Blumberg, B. (2003) · Environmental Health Perspectives · doi:10.1289/ehp.6560 · Cited by 133 · see citing works
Chowbay, B., Zhou, S., & Lee, E. J. D. (2005) · Drug Metabolism Reviews · doi:10.1081/dmr-28805 · Cited by 119 · see citing works
Alternatively spliced isoforms of the human constitutive androstane receptor
Auerbach, S. S. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg419 · Cited by 120 · see citing works
Sharoni, Y., Danilenko, M., Dubi, N., Ben-Dor, A., & Levy, J. (2004) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2004.03.009 · Cited by 119 · see citing works
Identification of an endogenous ligand that activates pregnane X receptor-mediated sterol clearance
Dussault, I., Yoo, H., Lin, M., Wang, E., Fan, M. Q., BATTA, A. K., Salen, G., Erickson, S. K., & FORMAN, B. M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0336235100 · Cited by 117 · see citing works
Zhou, C., Tabb, M. M., Sadatrafiei, A., Grün, F., & Blumberg, B. (2004) · Drug Metabolism and Disposition · doi:10.1124/dmd.104.000299 · Cited by 114 · see citing works
FOOD-DRUG INTERACTIONS VIA HUMAN CYTOCHROME P450 3A (CYP3A)
Fujita, K. (2004) · Drug metabolism and drug interactions · doi:10.1515/dmdi.2004.20.4.195 · Cited by 112 · see citing works
Baxter, J. D., Webb, P., Grover, G. J., & Scanlan, T. S. (2004) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2004.03.008 · Cited by 109 · see citing works
Nuclear Receptors in Drug Metabolism, Drug Response and Drug Interactions
Prakash, C., Zuniga, B., Song, C. S., Jiang, S., Cropper, J. D., Park, S.-G., & Chatterjee, B. (2015) · Nuclear Receptor Research · doi:10.11131/2015/101178 · Cited by 105 · see citing works
Shiraki, T., Sakai, N., Kanaya, E. N., & Jingami, H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212859200 · Cited by 100 · see citing works
Rencurel, F., Stenhouse, A., Hawley, S. A., Friedberg, T., Hardie, D. G., Sutherland, C. D., & Wolf, C. R. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m412711200 · Cited by 100 · see citing works
Kojima, H., Sata, F., Takeuchi, S., Sueyoshi, T., & Nagai, T. (2010) · Toxicology · doi:10.1016/j.tox.2010.11.008 · Cited by 94 · see citing works
Ekins, S., Mirny, L. A., & Schuetz, E. G. (2002) · Pharmaceutical Research · doi:10.1023/a:1021429105173 · Cited by 91 · see citing works
Substrate specificities of rat oatp1 and ntcp: implications for hepatic organic anion uptake
Hata, S., Wang, P., Eftychiou, N., Ananthanarayanan, M., BATTA, A. K., Salen, G., Pang, K. S., & Wolkoff, A. W. (2003) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00352.2002 · Cited by 89 · see citing works
Nuclear receptors as drug targets in cholestasis and drug-induced hepatotoxicity
Zollner, G., Wagner, M., & Trauner, M. A. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.03.005 · Cited by 89 · see citing works
Pregnane X receptor prevents hepatorenal toxicity from cholesterol metabolites
Sonoda, J., Chong, L.-W., Downes, M., Barish, G. D., Coulter, S., Liddle, C., Lee, C., & Evans, R. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409481102 · Cited by 89 · see citing works
Self-citationThe role of pregnane X receptor (PXR) in substance metabolism
Lv, Y., Luo, Y., Ren, H., Li, C., Xiang, Z.-X., & Luan, Z. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.959902 · Cited by 85 · see citing works
Petrick, J. S., & Klaassen, C. D. (2007) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.015974 · Cited by 85 · see citing works
Min, G., Kemper, J. K., & KEMPER, B. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200051200 · Cited by 83 · see citing works
Wang, H., Faucette, S. R., Gilbert, D., Jolley, S. L., Sueyoshi, T., Negishi, M., & LeCluyse, E. L. (2003) · Drug Metabolism and Disposition · doi:10.1124/dmd.31.5.620 · Cited by 83 · see citing works
Shenoy, S. D., Spencer, T. A., Mercer-Haines, N. A., Alipour, M., Gargano, M. D., Runge‐Morris, M., & Kocarek, T. A. (2004) · Drug Metabolism and Disposition · doi:10.1124/dmd.32.1.66 · Cited by 82 · see citing works
Krasowski, M. D., Yasuda, K., Hagey, L. R., & Schuetz, E. G. (2005) · Nuclear Receptor · doi:10.1186/1478-1336-3-2 · Cited by 80 · see citing works
Modifying chromatin to permit steroid hormone receptor-dependent transcription
Kinyamu, H. K., & Archer, T. (2003) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/j.bbaexp.2003.09.015 · Cited by 78 · see citing works
Chen, J., Kinyamu, H. K., & Archer, T. (2005) · Molecular Endocrinology · doi:10.1210/me.2005-0192 · Cited by 76 · see citing works
Dickmann, L. J., & Isoherranen, N. (2012) · Drug Metabolism and Disposition · doi:10.1124/dmd.112.047118 · Cited by 74 · see citing works
Pregnane X Receptor Protects HepG2 Cells from BaP-Induced DNA Damage
Naspinski, C., Gu, X., Zhou, G.-D., Mertens‐Talcott, S. U., Donnelly, K. C., & Tian, Y. (2008) · Toxicological Sciences · doi:10.1093/toxsci/kfn058 · Cited by 73 · see citing works
Knight, T. R., Choudhuri, S., & Klaassen, C. D. (2008) · Toxicological Sciences · doi:10.1093/toxsci/kfn179 · Cited by 72 · see citing works
Hormones in international meat production: biological, sociological and consumer issues
Galbraith, H. (2002) · Nutrition Research Reviews · doi:10.1079/nrr200246 · Cited by 72 · see citing works
Mani, S., Huang, H., Sundarababu, S., Liu, W., Kalpana, G. V., Smith, A. B., & Horwitz, S. B. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-0252 · Cited by 70 · see citing works
AhR, PXR and CAR: From Xenobiotic Receptors to Metabolic Sensors
Rakateli, L., Huchzermeier, R., & van der Vorst, E. P. C. (2023) · Cells · doi:10.3390/cells12232752 · Cited by 68 · see citing works
Can flies help humans treat neurodegenerative diseases?
Marsh, J., & Thompson, L. M. (2004) · BioEssays · doi:10.1002/bies.20029 · Cited by 68 · see citing works
A brief history of the discovery of PXR and CAR as xenobiotic receptors
Yan, J., & Xie, W. (2016) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2016.06.011 · Cited by 67 · see citing works
Self-citationXenobiotic-sensing nuclear receptors involved in drug metabolism: a structural perspective
Wallace, B. D., & Redinbo, M. R. (2012) · Drug Metabolism Reviews · doi:10.3109/03602532.2012.740049 · Cited by 66 · see citing works
Chen, Q. M., Alexander, D., Sun, H., Xie, L., Lin, Y., Terrand, J., Morrissy, S., & Purdom, S. (2005) · Molecular Pharmacology · doi:10.1124/mol.104.003814 · Cited by 66 · see citing works
Jacobs, M. N., Dickins, M., & Lewis, D. F. V. (2003) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(03)00021-9 · Cited by 65 · see citing works
Human PXR Forms a Tryptophan Zipper-Mediated Homodimer
Noble, S. M., Carnahan, V. E., Moore, L. B., Luntz, T., Wang, H., Ittoop, O. R. R., Stimmel, J. B., Davis-Searles, P. R., Watkins, R. E., Wisely, G. B., et al. (2006) · Biochemistry · doi:10.1021/bi0602821 · Cited by 63 · see citing works
Baker, M. E. (2005) · Integrative and Comparative Biology · doi:10.1093/icb/45.1.172 · Cited by 57 · see citing works
The Biochemistry of Drug Metabolism – An Introduction
Krämer, S. D., & Testa, B. (2008) · Chemistry & Biodiversity · doi:10.1002/cbdv.200890214 · Cited by 59 · see citing works
Therapeutic potential of Liver Receptor Homolog-1 modulators
Lazarus, K. A., Wijayakumara, D., Chand, A. L., Simpson, E. R., & Clyne, C. D. (2012) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2011.12.017 · Cited by 58 · see citing works
Master regulation of bile acid and xenobiotic metabolism via the FXR, PXR and CAR trio
Modica, S. (2009) · Frontiers in bioscience · doi:10.2741/3563 · Cited by 57 · see citing works
Modulation of Bile Acid Metabolism by 1α-Hydroxyvitamin D3 Administration in Mice
Nishida, S., Ozeki, J., & Makishima, M. (2009) · Drug Metabolism and Disposition · doi:10.1124/dmd.109.027334 · Cited by 54 · see citing works
Nuclear receptor superfamily: Principles of signaling
Germain, P., Altucci, L., Bourguet, W., Rochette-Egly, C., & Gronemeyer, H. (2003) · Pure and Applied Chemistry · doi:10.1351/pac200375111619 · Cited by 53 · see citing works
Chen, S., Yueh, M., Evans, R. M., & Tukey, R. H. (2012) · Hepatology · doi:10.1002/hep.25671 · Cited by 53 · see citing works
Self-citationEffect of organophosphate pesticide diazinon on expression and activity of intestinal P-glycoprotein
Lecoeur, S., Videmann, B., & Mazallon, M. (2005) · Toxicology Letters · doi:10.1016/j.toxlet.2005.09.003 · Cited by 53 · see citing works
Consequences of psychophysiological stress on cytochrome P450-catalyzed drug metabolism
Konstandi, M., Johnson, E. O., & Lang, M. A. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.05.011 · Cited by 54 · see citing works
The environmental estrogen, nonylphenol, activates the constitutive androstane receptor
Hernandez, J. P., Huang, W., Chapman, L. M., Chua, S., Moore, D. D., & Baldwin, W. S. (2007) · Toxicological Sciences · doi:10.1093/toxsci/kfm107 · Cited by 52 · see citing works
Sueyoshi, T., Moore, R., Sugatani, J., Matsumura, Y., & Negishi, M. (2008) · Molecular Pharmacology · doi:10.1124/mol.107.042960 · Cited by 52 · see citing works
Pharmaceutical use of mouse models humanized for the xenobiotic receptor
Xie, W., & Evans, R. M. (2002) · Drug Discovery Today · doi:10.1016/s1359-6446(02)02251-1 · Cited by 52 · see citing works
Self-citationLiu, J., Chen, Z., Chen, H., Hou, Y., Lu, W., He, J., Tong, H., Zhou, Y., & Cai, W. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18030603 · Cited by 50 · see citing works
Shabbir, A., DiStasio, S., Zhao, J., Cardozo, C. P., Wolff, M. S., & Caplan, A. J. (2004) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2004.07.011 · Cited by 49 · see citing works
Application of In Vitro Metabolism Activation in High-Throughput Screening
Ooka, M., Lynch, C., & Xia, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218182 · Cited by 49 · see citing works
Bock, K. W., & Köhle, C. (2004) · Drug Metabolism Reviews · doi:10.1081/dmr-200033455 · Cited by 49 · see citing works
Qin, S., Chen, J., Tanigawa, S., & Hou, D. (2012) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201200563 · Cited by 47 · see citing works
Pregnane X Receptor and the Gut-Liver Axis: A Recent Update
Dutta, M., Lim, J. J., & Cui, J. Y. (2021) · Drug Metabolism and Disposition · doi:10.1124/dmd.121.000415 · Cited by 46 · see citing works
Yamaguchi, H., Hishinuma, T., Endo, N., Tsukamoto, H., Kishikawa, Y., Masugi, S. A. T. O., MURAI, Y., Hiratsuka, M., Ito, K., Okamura, C., et al. (2006) · International Journal of Gynecological Cancer · doi:10.1111/j.1525-1438.2006.00593.x · Cited by 45 · see citing works
Investigation of the mechanism of triclosan induced mouse liver tumors
Wang, Z., Li, X., & Klaunig, J. E. (2017) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2017.03.001 · Cited by 43 · see citing works
Zhang, G., Ou, R., Li, F., Wu, J., Zheng, L., Tong, Y., Liu, Y., Liu, Z., & Lu, L. (2016) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2016.01.031 · Cited by 42 · see citing works
Handschin, C., Blättler, S. M., Roth, A. B., Looser, R., Oscarson, M., Kaufmann, M., Podvinec, M., Gnerre, C., & Meyer, U. (2004) · Nuclear Receptor · doi:10.1186/1478-1336-2-7 · Cited by 42 · see citing works
Tierney, K. B., Kennedy, C. J., Gobas, F. A. P. C., Gledhill, M., & Sekela, M. A. (2013) · Fish physiology · doi:10.1016/b978-0-12-398254-4.00001-7 · Cited by 41 · see citing works
Jørgensen, A., Giessing, A. M. B., Rasmussen, L. J., & Andersen, O. (2005) · Environmental Toxicology and Chemistry · doi:10.1897/05-047r.1 · Cited by 41 · see citing works
Matsunawa, M., Akagi, D., Uno, S., Endo‐Umeda, K., Yamada, S., Ikeda, K., & Makishima, M. (2012) · Drug Metabolism and Disposition · doi:10.1124/dmd.112.046839 · Cited by 40 · see citing works
- Authors
- Xie, W., & Evans, R. M.
- Affiliations
- Salk Institute for Biological Studies (US)
- Corresponding author
- Xie, Wen
- Evans, Ronald M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-10
- Volume
- 276
- Issue
- 41
- Pages
- 37739-37742
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1983836083
- Cited by
- 210
- References
- 25
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 5 · 2017: 7 · 2016: 7 · 2015: 5 · 2014: 4 · 2013: 3 · 2012: 18
- FWCI
- 17.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- orphan nuclear receptor, xenobiotics, cytochrome P450, drug metabolism, CYP3A4, pregnane X receptor, constitutive androstane receptor, retinoid X receptor, drug-drug interactions, drug repurposing, drug toxicity
- MeSH terms
- Animals, Humans, Xenobiotics, Genome, Human, Receptors, Cytoplasmic and Nuclear, Receptor Cross-Talk
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
